Salmonella typhi, a causative agent of typhoid fever is raising a major threat due to its potential use in bioterrorism [Synder J W, American Society of Microbiology; 2000] and the non-availability of an efficient candidate vaccine. Salmonella species colonize several different host species. Some of the Salmonella species cause infections in specific hosts, whereas other Salmonella species have broad host range. S. typhi and paratyphi are strict pathogens of human. S. dublin cause disease in cattle, S. abortus-equi causes abortion in horses. S. abortus-ovi causes abortion in sheep. S. choleraesuis is major cause of lethal diarrhea in young pigs. S. typhimurium and S. enteritidis cause salmonellosis in human, poultry, pigs, cattle and rodents; S. arizonae causes disease in turkeys, whereas S. gallinarum causes salmonellosis only in poultry.
About 21.6 million people have suffered from typhoid and over 216,500 have succumbed to it, globally, in the year 2000 alone [Crump J A et. al. Bull World Health Organ 2004]. The incidence of typhoid is high (>100 cases per 100,000 population each year) in south-central Asia, southeast Asia and possibly southern Africa (10-100 cases per 100,000) [WHO 2004]. The increased appearance of antibiotic resistant strains of Salmonella further complicates the situation [Bhan M K et al., Lancet 2005].
The key to success for many bacteria in causing infection is colonization of host tissues. An enteric bacterium, such as Salmonella, gains entry through the oral route and survives the harsh environment of the intestine. At the intestinal mucosa, these bacteria encounter host defense mechanisms including antimicrobial peptides (AMPs), which are cationic, amphipathic molecules that kill bacteria by membrane permeabilization. Within the intestine, AMPs are secreted into the lumen by Paneth cells located in the base of intestinal crypts. AMPs are also found within phagocytic cells located in the intestinal submucosa. The ability of Salmonella to survive within the host intestine and within professional phagocytes is likely to depend, at least in part, on mechanisms of resistance to AMPs. The Pmr systems in Salmonella which includes pmrHIFJKLM, pmrD, pmrA-B, pmrE and pmrG are known to modify LPS, confer resistance to antimicrobial peptides and to regulate other two component regulatory system [Eguchi Y, et. al. Trends Biochem Sci 2005; 30: 70-2].
The Salmonella vaccine strains created so far had mutations in the metabolic genes or pathogenicity islands. Salmonella harboring mutations in SPI2 [Kirkpatrick B D, et. al. 2006 Vaccine 24:116-23], aro A [Khan S A, et. al. Vaccine 2006; 21:538-48.], hrtA [Tacket C O, Infect Immun 1997; 65:452-6] have been tested as a vaccine candidates in both animal models and humans. These vaccine candidates have not been able to fully protect the animals. The only licensed attenuated live oral typhoid vaccine, S. typhi strain Ty21a, is well tolerated and immunogenic, but requires three or four spaced doses of 2-6×109 CFU given every other day, an important practical shortcoming [Ivanoff B et. al. Bull WHO 1994; 72:957.26.]. Ty800, a vaccine strain, where phoP gene was knocked out, exhibited excellent protection in human volunteers [Miller S I, et. al. Vaccine 1993; 11(2): 122-5].
Previous literature shows mutated strains of Salmonella enterica serovar Typhimurium lacking pmrG-HM-D being studied (Negi V. D. et al, Vaccine. 2007 Jul. 20; 25(29):5315-23. Epub 2007 Jun. 4). However the model of experiment was a murine typhoid model against Salmonellosis caused by the organism.
Typhoid fever resulting from infection by Salmonella typhi, is a life threatening disease. An alarming increase in the antibiotic resistance and non-availability of a suitable vaccine further complicates the situation. Further, the threat to the pregnant women upon Salmonella typhi infection exists which involves loss of fetus or miscarriage.
Vi induces only short-lived antibody responses in children 2 to 5 years of age (unpublished data) and does not elicit protective levels in children younger than 2 years; in adults, reinjection after 2 years restores the level of vaccine-induced Vi antibody but does not elicit a booster response. These age-related and T-independent immunologic properties are similar to those of most polysaccharide vaccines.
Vi polysaccharide is coded by SPI7 island (Salmonella Pathogenecity Island 7). SPI7 is a mobile island and not all the strain of S. typhi harbors SPI7. Hence, it is not a good idea to develop vaccine against Vi, which is not found in all strains of S. typhi. 
According to Prof Stefan Kaufmann, who is heading the Bill and Melinda Gates foundation, vaccine development project, reported that till now there is no efficient vaccine against S typhi. 
With more than 16 millions of individuals getting infected with S. typhi each year, the threat continues to increase. Salmonella typhi has been classified as one of the organism for bioterrorism because of its life threatening extra-intestinal infection.
Keeping in mind the shortcomings, it is very important to generate a vaccine which can cover wide age groups, confer protective immunity and prevent abortion and still birth in pregnant females. The present invention thus covers and takes the appropriate measures to overcome the shortcomings reflected above.